The thrombospondins (TSP) are extracellular matrix proteins with diverse functions, including immune regulation. In the CNS, TSP is poorly expressed in the two areas most damaged by autoimmune lesions in multiple sclerosis and in its experimental model, EAE (e.g., the spinal cord and the optic nerve). Thus, this molecule might be employed by the CNS in fighting off autoimmune inflammation. Based on mounting evidence, including our preliminary findings, that TSP-1 suppresses the proliferation of inflammatory T cells and confers them with regulatory properties, we now propose to carry out in vivo and in vitro studies to investigate (i) the temporal and regional pattern of TSP-1 expression by resident cells in the CNS of healthy and EAE-inflicted animals; (ii) a potential role for TSP-1 expression in preventing the onset and/or in contributing to the induction of remission in EAE; (iii) and whether inflammatory cytokines affect TSP-1 expression by resident CNS cells. These studies will help determine whether TSP-1 plays a role in preventing autoimmune inflammation in the central nervous system (CNS), and can potentially uncover a new candidate molecule to be used as a therapy for the treatment of autoimmune diseases of the CNS.